The biochemical differentiation of the fetal fibroblast as related to its growth requirements in vitro is under study. Reliable and reproducible methods are being sought to grow sufficient numbers of cells in culture to make early prenatal diagnosis possible, and to provide normative biochemical data to identify the mutant cell from its normal counter-part. The specific goals of the multidisciplinary research program are: 1) to define the chemical and physical conditions for the optimal growth in vitro of fetal cells obtained by amniocentesis at various stages of gestation, 2) to ascertain the metabolic parameters of the cells, and 3) to study selected variables which may alter the biochemical expression of the fetal cell, and 4) concomitantly apply data obtained in these studies to prenatal diagnosis for the prevention of mental retardation. The methods used in these studies combine cell culture with isotopic and microchemical analyses of the fetal cell.